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United States Patent | 5,719,271 |
Cook ,   et al. | February 17, 1998 |
Covalent cross-linkages for two oligonucleotide strands or for first and second regions of a single oligonucleotide strand connect sugar moieties of nucleotides on the respective strands or the regions of the single strand. The cross-linkages are connected to at least one strand or region via a space-spanning group. The cross-linkage also can be connected to the other strand or other region via a space-spanning group or via an abasic site located on the other strand or other region.
Inventors: | Cook; Phillip Dan (Carlsbad, CA); Manoharan; Muthiah (Carlsbad, CA); Bruice; Thomas (Carlsbad, CA) |
Assignee: | ISIS Pharmaceuticals, Inc. (Carlsbad, CA) |
Appl. No.: | 295743 |
Filed: | August 30, 1994 |
Current U.S. Class: | 536/23.1; 536/24.3; 536/24.5 |
Intern'l Class: | C07H 021/00; C07H 021/02; C07H 021/04 |
Field of Search: | 435/6,375 514/44 536/23.1,24.1,24.3,24.5,25.3 |
4123610 | Oct., 1978 | Summerton et al. | 536/25. |
4868103 | Sep., 1989 | Stavrianopoulos | 435/5. |
5138045 | Aug., 1992 | Cook et al. | 536/24. |
5223618 | Jun., 1993 | Cook et al. | 544/276. |
5378825 | Jan., 1995 | Cook et al. | 536/25. |
5399676 | Mar., 1995 | Froehler | 536/23. |
5543507 | Aug., 1996 | Cook et al. | 536/23. |
Foreign Patent Documents | |||
WO 91/14436 | Mar., 1991 | WO. | |
WO 91/00243 | Oct., 1991 | WO. |
"Instructions to Authors for Bioconjugate Chemistry" Bioconjugate Chem. vol. 6, No. 1, p. 5A Jan. 1995. Gura, "Antisense has Growing Pains" Science, vol. 270, pp. 575-577, Oct. 1995. Zon et al. "Phosphorothioate Oligonucleotides in Oligonucleotides and Analogues", F. Eckstein, ed. IRL press, New York, pp. 87-108, 1991. Matteucci et al, Tetrahedron Letters, vol. 28, pp. 2469-2472, 1987. Meyer et al, J. Am. Chem. Soc, vol. 11, pp. 8517-8519, 1989. Stein et al, Science, vol. 261, pp. 1009-1012, 1993. Webb et al, Nuc. Acids Res, vol. 14, pp. 7661-7574, 1986. Akiyama, et al., "The Selective Protection of Uridine with a p-Methoxybenzyl Chloride: A Synthesis of 2'-O-Methyluridine", Chem. Soc. Japan 63:3356-3357 (1990). Bartel et al., "HIV-1 rev regulation involves recognition of non-Watson-Crick base pairs in viral RNA", Cell, 67:529-536, 1991. Bertrand et al., "Synthesis, thermal stability And reactivity twoards 9-aminoellipticine of double-stranded oligonucleotides containing a true abasic site", Nucleic Acids Research, 17, 10307-10319, 1989. Butke et al., "Facile Synthesis of 2'-Amino-2-deoxynucleoside from the Corresponding Arabino Derivative", J. Carbohydrates.Nucleosides.Nucleotides 1980 7(1), 63. Chang et al., "Periodate-oxidized AMP as a substrate, an inhibitor and an affinity label of human placental alkaline phosphate", Biochem. J. 199:281-287 (1981). Cowart et al., A novel combined chemical-enzymatic synthesis of cross-linked dna using a nucleoside triphosphate analogue, Biochemistry, 30, 788-796, 1991. Dartmann et al., "Short Communications: The Nucleotide Sequence and Genome Organization of Human Papilloma Virus Type 11", Virology 151:124-130 (1986). Divakar et al., "Approaches to the Synthesis of 2'-Thio Analogues of Pyrimidine Ribosides", J.Chem.Soc.Perkin.Trans. 1:969-974 (1990). Easterbrook-Smith et al., "Pyruvate Carboxylase: Affinity Labelling of the Magnesium Adenosine Triphosphate Binding Site", Eur. J. Biochem, 62:125-130 (1976). Farahani et al., "Hydroxyl Radical Induced Cross-Linking Between Phenylalanine and 2-Deoxyribose", Biochemistry 27(13) :4695-4698 (1988). Ferentz, A.E. and Verdine, G.L., "Disulfide Cross-Linked Oligonucleotides", J. Am. Chem. Soc. 113:4000-4003 (1991). Fiandor, J. and Tam, S.Y., "Synthesis of 3'-Deoxy-3'-(Propynyl) Thymidine and 3'-Cyanomethyl-3'-Deoxythymidine, Analogs of AZT", Tetrahedron Letters 31:597-600 (1990). Francois, et al., "Flexible Aglycone Residues in Duplex DNA", Tetrahedron Letters 31:6347-6350 (1990). Grineva, N.I. and Karpova, G.G., "Complementarily Addressed Modification of rRNa With p-(Chloroethylmethylamino) Benzylidene Hexanucleotides", FEBS Letters 32:351-355 (1973). Groebke and Leumann, "A method for preparing oigodeoxynucleotides containing an apurinic site", Helvetica Chimica Acta 73:608 (1990). Meyer et al., "Efficient, Specific Cross-Linking and Cleavage of DNA by Stable, Synthetic Complementary Oligodeoxynucleotides", J.Am.Chem.Soc., 11:8517-8519 (1989). Hall et al., Synthetic Procedures in Nucleic Acid Chemistry, Zorbach and Tipson, editors, vol. 1, John Wiley & Sons 1968. Hansske et al., 2' And 3'-ketonucleosides and their Arabino and Xylo reduction products, Tetrahedron, 40, 125-135, 1984. Heaphy et al., "HIV-1 Regulator of Virion Expression (rev) Protein Binds to an RNA Stem-loop Structure Located Within the Rev Response Element Region", Cell, 60:685-693, 1990. Hegde et al., "Crystal Structure at 1..7 A of the bovine papillomavirus-1 E2 DNA-binding domain bound to its DNA target", Nature 359:505-512 (1992). Horn, T. et al., "Controlled chemical cleavage of synthetic DNA at specific sites", Nucleosides & Nucleotides, 10:299 (1991). Iyer et al., "Abasic oligodeoxyribonucleoside phosphorothioates synthesis and evaluation as anti-HIV-1 agents", Nucleic Acids Research, 18:2855-2859, 1990. Knorre et al., Nucleotide and Oligonucleotide Derivatives as Enzyme and Nucleic Acid Targeted Irreversible Inhibitors, Chemical Aspects, G. Weber (Ed.), Advances Press, Oxford, pp. 277-320 (1986). Lee et al., "Interaction of Psoralen-Derivatized Oligodeoxyribonucleoside Methylphosphonates with Single-Stranded DNA", Biochemistry 27:3197-3203 (1988). Lemaitre et al., "Specific antiviral activity of a poly(L-lysine)-conjugated oligodeoxyribonucleotide sequence complementary to vesicular stomatitis virus N protein mRNA initiation site", Proc.Natl.Acad.Sci. USA 84:648-652 (1987). Lindahl et al., "DNA N-Glycosidases: Properties of Uracil-DNA glycosidase from Escherichia coli", J.Biol.Chem. 252:3286-3294 (1977). Manoharan et al., "Coexistence of Conformations in a DNA Heteroduplex Revealed by Site Specific Labeling with .sup.13 C-Labeled Nucleotides", J.Am.Chem.Soc. 109:7217-7219 (1987). Manoharan et al., "Introduction of a Lipophilic Thioether Tether in the Minor Groove of Nucleic Acids for Antisense Applications", Biorganic & Medicinal Chemistry Letters 3:2765-2770 (1993). Manoharan et al. "Mechanism of UV Endonuclease V Cleavage of Abasic Sites in DNA Determined by .sup.13 C Labeling", J.Am.Chem.Soc. 110:2690-2691 (1988). Matteucci et al., "Synthesis and Crosslinking Properties of a Deoxyoligonucleotide Containing N.sup.6,N.sup.6 -Ethanodeoxyadenosine", Tetra.Ltrs. 28:2469-2472 (1987). McArthur et al., "Amino Group Blocking. Improved Method for N-Phthaloylation Using N-(Ethoxycarbonyl)Phthalimide", Synthetic Communications 13: 311-318 (1983). Nucleic Acids in Chemistry and Biology, Blackburn and Gait, eds., Oxford University Press, New York, 1991. (pp. 52-58 only). Pfitzner and Moffatt, "Sulfoxide-carbodiimide reactions. I. A facile oxidation of alcohols", Journal of American Chemical Society 87(24) :5661-5670 (1965). Ratner, "Can the antisense message be delivered", Biotechnology, 7, 207, 1989. Peoch'h, D. et al., "Efficient chemical synthesis of oligodeoxynucleotides containing a true abasic site", Tetrahedron Letters 32:207 (1991). Sproat et al., "New synthetic routes to protected purine 2'-O-methylriboside-3'-O-phosphoramidites using a novel alkylation procedure", Nucleic Acids Research 18:41-49 (1990). Sproat et al., "New synthetic routes to synthons suitable for 2'-O-allyloligoribonucleotide assembly", Nucleic Acids Research, 19:733 (1991). Stein et al., "Antisense oligonucleotides as therapeutic agents--is the bullet really magical?" Science 261:1009-1012 (1993). Summerton et al., "Sequence-specific Crosslinking Agents for Nucleic Acids", J.Mol. Biol. 122:145-162 (1978). Summerton, J., "Sequence-Specific Crosslinking Agents for Nucleic Acids: Design and Functional Group Testing", J. Theor.Biol. 78:61-75 (1979). Vasseur, Jean-Jacques et al., "Apurinic DNA: Modelisation and Reactivity Towards 9-Aminoellipticine and Related Amines", Nucleosides & Nucleotides 8(5&6) :863-866 (1989). Wagner et al., "Preparation and synthetic utility of some organotin derivatives of nucleosides", J. Org. Chem., 39:24 (1974). "Webb and Matteucci., Hybridization triggered cross-linking of deoxyoligonucleotides", Nucleic Acids Research, 14, 7661-7674, 1986. |
______________________________________ T.sub.m ______________________________________ Oligomer 5 - Oligomer 1 duplex (wild type) 48.degree. C. Oligomer 5 - Oligomer 2 duplex (abasic site) <30.degree. C. Oligomer 5 - Oligomer 2 Cross-linked Strands I 74.degree. C. ______________________________________
__________________________________________________________________________ SEQUENCE LISTING (1) GENERAL INFORMATION: (iii) NUMBER OF SEQUENCES: 26 (2) INFORMATION FOR SEQ ID NO:1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: 2'-deoxy uridine nucleotide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: CGCAGUCAGCC11 (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: abasic site (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: CGCAGNCAGCC11 (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:9 (D) OTHER INFORMATION: 2'- deoxyuridine nucleotide (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:18 (D) OTHER INFORMATION: 2'- deoxyuridine nucleotide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: GACAGAGGUAGGAGAAGUGA20 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:9 (D) OTHER INFORMATION: abasic site (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:18 (D) OTHER INFORMATION: abasic site (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: GACAGAGGNAGGAGAAGNGA20 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: 2'-O- (pentylamino)adenosine nucleotide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: GGCTGACTGCG11 (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:9 (D) OTHER INFORMATION: nucleotide modified to incorporate a pentylamino functionality (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:18 (D) OTHER INFORMATION: nucleotide modified to incorporate a pentylamino functionality (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: CTGTCTCCATCCTCTTCACT20 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:4 (D) OTHER INFORMATION: nucleotide modified to incorporate a dodecylamino functionality (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: GGCTGACTGCG11 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: nucleotide modified to incorporate a butylamino functionality (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: GGCTGACTGCG11 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: nucleotide modified to incorporate a allylamine functionality (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: GGCTGACTGCG11 (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: nucleotide modified to incorporate a 2'-O-(octylhydrazino) functionality (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: GGCTGUCTGCG11 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:8 (D) OTHER INFORMATION: uridine nucleotide having a 2'-O- (octylhydrazine) group (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:19 (D) OTHER INFORMATION: guanosine nucleotide having a 2'-O- (octylhydrazine) group (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: AGCCAGAUCUGAGCCUGGGAGCUCUCUGGCU31 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: nucleotide modified to incorporate a octyl-hydroxylamine functionality (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: GGCTGUCTGCG11 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: nucleotide modified to incorporate a pentyl-N-semicarbazide functionality (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: GGCTGUCTGCG11 (2) INFORMATION FOR SEQ ID NO:14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: nucleotide modified to incorporate an ethyl hydrazide functionality (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: GGCTGUCTGCG11 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: nucleotide modified to incorporate a heptan-7-ol functionality (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: GGCTGUCTGCG11 (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:12 (D) OTHER INFORMATION: adenosine nucleotide having a 2'-O- (pentylamino) group (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:23 (D) OTHER INFORMATION: uridine nucleotide having a 2'-O-›propion-4-al bis(o-nitrobenzyl) acetal! group (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: AGCCAGAUCUGAGCCUGGGAGCUCUCUGGCU31 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:1 (D) OTHER INFORMATION: adenosine nucleotide having a 2'-O-›S-trityl(hexyl-8-thiol)!group (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:31 (D) OTHER INFORMATION: uridine nucleotide having a 2'-O-›S- trityl(hexyl-8-thiol)!group (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: AGCCAGAUCUGAGCCUGGGAGCUCUCUGGCU31 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 base pairs (B) TYPE: nucleic acid
(C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:9 (D) OTHER INFORMATION: 2'-O-›propion-3-al bis(o- nitrobenzyl) acetal!group (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:17 (D) OTHER INFORMATION: 2'-O-›propion-3-al bis(o- nitrobenzyl) acetal!group (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: GACAGAGGUAGGAGAAUGA19 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: guanosine nucleotide having a 2'-O-(›2-amylenyl!-N-phthalimide) group (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:25 (D) OTHER INFORMATION: uridine nucleotide having a 2'-O-›S- trityl(pentan-8-thiol)!group (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: AGCCAGAUCUGAGCCUGGGAGCUCUCUGGCU31 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:1 (D) OTHER INFORMATION: 2'-O- (eicosylamino)adenosine nucleotide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: AGCCAGAUCUGAGCCUGGGAGCUCUCUGGCU31 (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:1 (D) OTHER INFORMATION: 2'-O-›propion-3-al bis(o- nitrobenzyl) acetal!functionalized adenosine nucleotide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: AGCCAGAUCUGAGCCUGGGAGCUCUCUGGCU31 (2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:2 (D) OTHER INFORMATION: hexylamine modified uridine moiety (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: TUT3 (2) INFORMATION FOR SEQ ID NO:23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: 2'-O- (hexylamino) uridine nucleotide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: GGCTGUCTGCG11 (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: 2'-O- (hexylamino) uridine nucleotide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: GGCTGUCTGCG11 (2) INFORMATION FOR SEQ ID NO:25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: 2'- deoxyuridine (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: GGCTGUCTGCG11 (2) INFORMATION FOR SEQ ID NO:26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 11 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (A) NAME/KEY: Modified-site (B) LOCATION:6 (D) OTHER INFORMATION: abasic site (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: GGCTGNCTGCG11 __________________________________________________________________________